2-(3-{2-[((2R)-2-{4-benzyloxy-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]-2-methylpropyl}phenyl)-N-[(4'-hydroxybiphenyl-3-yl)methyl]-acetamide | 921598-25-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(3-{2-[((2R)-2-{4-benzyloxy-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]-2-methylpropyl}phenyl)-N-[(4'-hydroxybiphenyl-3-yl)methyl]-acetamide
• 英文别名: 2-[3-[2-[[(2R)-2-[tert-butyl(dimethyl)silyl]oxy-2-[3-(methanesulfonamido)-4-phenylmethoxyphenyl]ethyl]amino]-2-methylpropyl]phenyl]-N-[[3-(4-hydroxyphenyl)phenyl]methyl]acetamide
• CAS: 921598-25-6
• 化学式: C₄₇H₅₉N₃O₆SSi
• 分子量: 822.153
• InChiKey: DYQJRLGBWPNWMJ-SJARJILFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.54
• 重原子数：
  58
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(3-{2-[((2R)-2-{4-benzyloxy-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]-2-methylpropyl}phenyl)-N-[(4'-hydroxybiphenyl-3-yl)methyl]-acetamide 在 5%-palladium/activated carbon 、 氢气 作用下， 以 乙酸丁酯 、 乙酸乙酯 为溶剂， 60.0 ℃ 、400.01 kPa 条件下， 反应 24.0h， 生成 2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide
  参考文献：
  名称：

  Development of a Potential Manufacturing Route to PF-00610355: A Novel Inhaled β₂-Adrenoreceptor Agonist

  摘要：

  The development of a practical, scalable route to PF-00610355 (8) is described. In this convergent approach, amine 9 is coupled to protected bromohydrin 1 to give the doubly protected intermediate 26. TBS-Deprotection of 26 affords the benzyl protected penultimate intermediate 25 which is crystallized as the corresponding hemifumarate salt 25a. On the basis of solubility data, the final debenzylation was conducted in aqueous THF, and the API (8) is isolated from acetonitrile by an unusual distillative crystallization process. The development of an efficient process to prepare amine 9 is also described.

  DOI：

  10.1021/op2002408
• 作为产物：
  描述：

  dimethyl 2,2'-(1,3-phenylene)diacetate 在 lipolase 、 水 、 calcium acetate 、 碳酸氢钠 、 溶剂黄146 、 硫脲 、 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 四氢呋喃 、 异丁醇 、 乙酸丁酯 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 75.0h， 生成 2-(3-{2-[((2R)-2-{4-benzyloxy-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]-2-methylpropyl}phenyl)-N-[(4'-hydroxybiphenyl-3-yl)methyl]-acetamide
  参考文献：
  名称：

  [EN] INTERMEDIATE AND PROCESS FOR THE PREPARATION OF A SULFONAMIDE DERIVATIVE
  [FR] INTERMÉDIAIRE ET PROCÉDÉ DE PRÉPARATION D'UN DÉRIVÉ SULFONAMIDE

  摘要：

  该发明涉及一种结晶形式的2-氯-N-{2-[3-(2-{[(4'-羟基联苯-3-基)甲基]氨基}-2-氧乙基)苯基]-1,1-二甲基乙基}乙酰胺，以及其制备方法和在制备β2激动剂N-[(4'-羟基联苯-3-基)甲基]-2-(3-{2-[((2R)-2-羟基-2-{4-羟基-3-[(甲磺酰)氨基]苯基}乙基)氨基]-2-甲基丙基}苯基)乙酰胺中的应用，该激动剂在呼吸系统疾病治疗中有用。

  公开号：

  WO2013021309A1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF SULFONAMIDE DERIVATIVES<br/>[FR] PROCEDE POUR LA PREPARATION DE DERIVES DE SULFONAMIDE
  申请人：PFIZER LTD

  公开号：WO2007010356A3

  公开（公告）日：2007-08-23
• Optimization of the Manufacturing Route to PF-610355 (1): Synthesis of Intermediate <b>5</b>
  作者：Stéphane Content、Thomas Dupont、Nicolas M. Fédou、Julian D. Smith、Steven J. R. Twiddle

  DOI：10.1021/op300341n

  日期：2013.2.15

  Tertiary carbinamine 5 is an isolated intermediate in the synthesis of a novel, inhaled beta-2 adrenoreceptor agonist PF-610355. Process development for the key amide-formation and Ritter reactions, together with reaction understanding studies are discussed in context of the synthesis of S. The optimized process employed to manufacture 140 kg of 5 is described, and was shown to have superior metrics to the preliminary commercial route.
• [EN] INTERMEDIATE AND PROCESS FOR THE PREPARATION OF A SULFONAMIDE DERIVATIVE<br/>[FR] INTERMÉDIAIRE ET PROCÉDÉ DE PRÉPARATION D'UN DÉRIVÉ SULFONAMIDE
  申请人：PFIZER LTD

  公开号：WO2013021309A1

  公开（公告）日：2013-02-14

  The invention relates to a crystalline form of 2-chloro-N-2-[3-(2-[(4'-hydroxybiphenyl-3- yl)methyl]amino}-2-oxoethyl)phenyl]-1,1-dimethylethyl}acetamide, a process for preparing the same and its use in the preparation of the 2 agonist N-[(4'-hydroxybiphenyl-3- yl)methyl]-2-(3-2-[((2R)-2-hydroxy-2-4-hydroxy-3- [(methylsulfonyl)amino]phenyl}ethyl)amino]-2-methylpropyl} phenyl)acetamide which is useful in the treatment of respiratory diseases.

  该发明涉及一种结晶形式的2-氯-N-2-[3-(2-[(4'-羟基联苯-3-基)甲基]氨基}-2-氧乙基)苯基]-1,1-二甲基乙基}乙酰胺，以及其制备方法和在制备β2激动剂N-[(4'-羟基联苯-3-基)甲基]-2-(3-2-[((2R)-2-羟基-2-4-羟基-3-[(甲磺酰)氨基]苯基}乙基)氨基]-2-甲基丙基}苯基)乙酰胺中的应用，该激动剂在呼吸系统疾病治疗中有用。
• Development of a Potential Manufacturing Route to PF-00610355: A Novel Inhaled β₂-Adrenoreceptor Agonist
  作者：Pieter D. de Koning、Nieves Castro、Iain R. Gladwell、Natalie A. Morrison、Ian B. Moses、Maninder S. Panesar、Alan J. Pettman、Nicholas M. Thomson

  DOI：10.1021/op2002408

  日期：2011.11.18

  The development of a practical, scalable route to PF-00610355 (8) is described. In this convergent approach, amine 9 is coupled to protected bromohydrin 1 to give the doubly protected intermediate 26. TBS-Deprotection of 26 affords the benzyl protected penultimate intermediate 25 which is crystallized as the corresponding hemifumarate salt 25a. On the basis of solubility data, the final debenzylation was conducted in aqueous THF, and the API (8) is isolated from acetonitrile by an unusual distillative crystallization process. The development of an efficient process to prepare amine 9 is also described.